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硫化氢收缩大鼠脑动脉
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硫化氢收缩大鼠脑动脉
李森,平娜娜,肖雪,曹永孝
基金项目:高等学校博士学科点专项科研基金(20100201110054) 作者简介:李森(1984-),男,在读博士生,主要研究方向:血管药理学 通信联系人:曹永孝(1957-),男,博士生导师,主要研究方向:血管药理学;中药组分与作用靶点;环境疾病与受体研究.

(西安交通大学医学院,西安 710061)

摘要:目的 新的气体信号分子硫化氢对脑血管的作用尚不明确,本文研究硫化氢收缩大鼠脑血管的作用及其机制。方法 用NaHS作为硫化氢供体,用微血管张力描记仪记录血管张力,用硫电极法测定硫化氢含量。结果 NaHS可浓度依赖性地收缩大鼠脑基底动脉;β2受体激动剂沙丁胺醇、腺苷酸环化酶抑制剂毛喉素均可增强NaHS对脑基底动脉的收缩作用,NaHS孵育可减弱沙丁胺醇或毛喉素对5-HT预收缩脑基底动脉的舒张作用;α2受体阻断剂萝芙素、cAMP类似物8B-cAMP均可减弱NaHS对脑基底动脉的收缩作用;一氧化氮合酶抑制剂L-NAME可增强NaHS对脑基底动脉的收缩作用,在L-NAME存在下,NaHS则可以减弱毛喉素对大鼠脑基底动脉的舒张作用;去除血管内皮可增强NaHS的脑血管收缩作用,而在毛喉素存在下,去除血管内皮会减弱NaHS的脑血管收缩作用;钾ATP通道阻断剂格列苯脲不影响NaHS对脑基底动脉的收缩作用。L型钙通道阻断剂硝苯地平可减弱NaHS对脑基底动脉的收缩作用。L型钙通道开放剂Bay K 8644不影响NaHS对脑基底动脉的收缩作用;与Krebs液相比,NaHS在不含碳酸氢根离子的HEPES液中的脑血管收缩作用减弱,而阴离子交换抑制剂DIDS和氧自由基抑制剂Tiron也可减弱NaHS对脑基底动脉的收缩作用。自发性高血压大鼠血浆和脑组织匀浆液中的硫化氢含量低于SD大鼠。结论 硫化氢可收缩大鼠脑基底动脉,这一作用可能与H2S降低脑血管平滑肌cAMP,调节碳酸氢根20 与氧自由基在细胞膜上的转运及随后氧自由基与NO的反应等机制有关。
关键词:药理学;硫化氢;脑动脉;环磷酸腺苷;血管收缩
中图分类号:R965
Hydrogen sulfide contracts rat cerebral artery in vitro
LI Sen, PING Nana, XIAO Xue, CAO Yongxiao
(College of Medicine,Xi'an Jiaotong University,Xi'an 710061)
Abstract: OBJECTIVE This study was designed to examine that vasoconstrictive effect of hydrogen sulfide, a new endogenous mediator on rat cerebral artery. METHODS NaHS was used as the donor of H2S. The vasoconstrictive effect of NaHS on rat cerebral artery was measured by wire myograph. H2S production was measured by sulfur electrode. RESULTS NaHS induced a concentration-dependently vasoconstriction on rat cerebral artery. Salbutamol, a β-adrenoceptor agonists, and forskolin, a selective adenylyl cyclase activator produced stronger vasoconstriction caused by NaHS on rat cerebral artery, respectively. Pretreatment with NaHS also significantly attenuated the vasorelaxant effect of salbutamol and forskolin on 5-HT precontracted rat cerebral  artery. Rauwolscine, a α2-adrenoceptor agonists, and 8B-cAMP, a cell permeable analog of cAMP produced weaker vasoconstriction caused by NaHS on rat cerebral artery, respectively. However, NaHS produced stronger vasoconstriction in the presence of L-NAME, a nitric oxide synthase inhibitor, or in the endothelium-denuded rat cerebral artery. NaHS also produced weaker vasodilation caused by forskolin in the presence of L-NAME but not in endothelium-denuded rat cerebral artery. Blockade of ATP-sensitive potassium channels with glibenclamide failed to attenuate the vasoconstriction induced by NaHS. Nifedpine, a specific L-type Ca2+ channel inhibitor, reduced the vasoconstriction caused by NaHS while Bay K 8644, a specific L-type Ca2+ channel agonist, failed to attenuate the vasoconstriction caused by NaHS on rat cerebral artery . In HEPES and Krebs buffers, the HCO3- dependent effect was specific to H2S. Blockade of anion  exchanger-2 activity with DIDS or with HCO3- free solution abolished the vasoconstrictive effect of NaHS. Tiron,a ROS scavenger, produced weaker vasoconstriction caused by NaHS on rat cerebral artery.The plasma H2S concentration and H2S production in brain tissues both decreased in SHR compared to SD rats. CONCLUSION H2S contracts rat cerebral artery. The vasoconstrictive effect of H2S may be involved in the adenyly cyclase/cAMP pathway. H2S also stimulates anion exchanger to transport extracellular HCO3- in exchange for intracellular superoxide anions which may further inactivate NO to induce vasoconstriction.
Key words: pharmacology; hydrogen sulfide ; cerebral artery ; cAMP; vasoconstrictive effect